A major goal of the neuroscience community is to develop treatment strategies that will slow or forestall the progression of chronic neurodegenerative diseases. Parkinson's disease (PD) is one of the most common adult neurodegenerative disorders, affecting over 1 million people in North America and the European Union. As a first step in identifying such therapies, the NINDS Exploratory Trials in Parkinson's disease (NET-PD) network successfully completed futility studies, which identified creatine as a potential agent to slow clinical decline in PD. The NET-PD network is now conducting a large, long-term, Phase 3 trial (known as LS1) comparing creatine to placebo. Our site #172 is one of the 50 NET-PD centers conducting the LS1 trial. In this renewal, we plan on continuing the execution of the trial at our center, enhance retention of enrolled subjects and complete the evaluations of all subjects enrolled at our site. All subjects are enrolled and the major effort isto enhance retention in order to test the primary hypothesis that daily administration of creatine (10 gm/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5 year follow-up visit against the background of dopaminergic therapy and best PD care. In addition, secondary measures of efficacy of creatine on individual PD measures will be assessed. We have implemented measures to enhance retention following uniform guidelines from the Clinical Coordinating Center. In addition, we have developed strategies that target the population at our site. These measures have been so far successful in retaining subjects past the 5 years of the trial.